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Andrea Schroll, Igor Theurl, Enrico Georgi, Sabine Zange, Thomas Rettenbacher, Rosa Bellmann-Weiler, Guenter Weiss
Tularaemia is a rare zoonotic disease caused by Francisella tularensis in humans. In Europe infections of humans and animals are mainly caused by F. tularensis subspecies holarctica. We report the first three documented cases of tularaemia in humans in Western Austria.
June 6, 2018: Ticks and Tick-borne Diseases
Qingmei Jia, Marcus A Horwitz
Francisella tularensis is the causative agent of tularemia and a Tier I bioterrorism agent. In the 1900s, several vaccines were developed against tularemia including the killed "Foshay" vaccine, subunit vaccines comprising F. tularensis protein(s) or lipoproteins(s) in an adjuvant formulation, and the F. tularensis Live Vaccine Strain (LVS); none were licensed in the U.S.A. or European Union. The LVS vaccine retains toxicity in humans and animals-especially mice-but has demonstrated efficacy in humans, and thus serves as the current gold standard for vaccine efficacy studies...
2018: Frontiers in Cellular and Infection Microbiology
Ingmar Janse, Rozemarijn Q J van der Plaats, Ana Maria de Roda Husman, Mark W J van Passel
Tularemia is an emerging zoonosis caused by the Gram-negative bacterium Francisella tularensis , which is able to infect a range of animal species and humans. Human infections occur through contact with animals, ingestion of food, insect bites or exposure to aerosols or water, and may lead to serious disease. F. tularensis may persist in aquatic reservoirs. In the Netherland, no human tularemia cases were notified for over 60 years until in 2011 an endemic patient was diagnosed, followed by 17 cases in the 6 years since...
2018: Frontiers in Cellular and Infection Microbiology
Olivier Duron, Olivier Morel, Valérie Noël, Marie Buysse, Florian Binetruy, Renaud Lancelot, Etienne Loire, Claudine Ménard, Olivier Bouchez, Fabrice Vavre, Laurence Vial
Mutualistic interactions with microbes have facilitated the radiation of major eukaryotic lineages [1, 2]. Microbes can notably provide biochemical abilities, allowing eukaryotes to adapt to novel habitats or to specialize on particular feeding niches [2-4]. To investigate the importance of mutualisms for the exclusive blood feeding habits of ticks, we focused on a bacterial genus of medical interest, Francisella, which is known to include both virulent intracellular pathogens of vertebrates [5, 6] and maternally inherited symbionts of ticks [7-9]...
May 22, 2018: Current Biology: CB
Fang-Yi Su, Jasmin Chen, Hye-Nam Son, Abby M Kelly, Anthony J Convertine, T Eoin West, Shawn J Skerrett, Daniel M Ratner, Patrick S Stayton
Pulmonary intracellular infections, such as tuberculosis, anthrax, and tularemia, have remained a significant challenge to conventional antibiotic therapy. Ineffective antibiotic treatment of these infections can lead not only to undesired side effects, but also to the emergence of antibiotic resistance. Aminoglycosides (e.g., streptomycin) have long been part of the therapeutic regiment for many pulmonary intracellular infections. Their bioavailability for intracellular bacterial pools, however, is limited by poor membrane permeability and rapid elimination...
May 31, 2018: Biomaterials Science
Akira Endo, Seiichi Toki
Sequence-specific nucleases (SSNs) are nowadays fundamental tools to generate mutants that impaired in genes of interest. The bioactive molecules screened in the chemical genomics studies affect specific physiological process by disrupting the function of its target protein(s). Mutation analysis of the gene(s) of target protein(s) of the screened chemical is necessary to resolve how the chemical works in plants. Clustered regularly interspersed short palindromic repeats (CRISPR) from Prevotella and Francisella 1 (Cpf1) are newly characterized RNA-directed endonuclease...
2018: Methods in Molecular Biology
Roberto De Pascalis, Andrew Hahn, Helen M Brook, Patrik Ryden, Nathaniel Donart, Lara Mittereder, Blake Frey, Terry H Wu, Karen L Elkins
There are no defined correlates of protection for any intracellular pathogen, including the bacterium Francisella tularensis, which causes tularemia. Evaluating vaccine efficacy against sporadic diseases like tularemia using field trials is problematic, and therefore alternative strategies to test vaccine candidates like the Francisella Live Vaccine Strain (LVS), such as testing in animals and applying correlate measurements, are needed. Recently, we described a promising correlate strategy that predicted the degree of vaccine-induced protection in mice given parenteral challenges, primarily when using an attenuated Francisella strain...
2018: PloS One
Erik Corona, Liuyang Wang, Dennis Ko, Chirag J Patel
Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS) to detect recent positive selection in genes that interact with proteins from 26 different pathogens...
2018: PloS One
Zhen-Hai Li, Min Liu, Feng-Qing Wang, Dong-Zhi Wei
OBJECTIVES: To test the applicability of Cpf1 from Francisella novivida in genomic integration of in vivo assembled DNA parts in Saccharomyces cerevisiae. RESULTS: An easy-to-use vector toolkit, containing a CEN6/ARS4 plasmid expressing Cpf1 from Francisella novivida (FnCpf1) and a 2 μ plasmid for crRNA or crRNA array expressing, was constructed for Cpf1-assisted genomic integration in S. cerevisiae. Our results showed that FnCpf1 allowed for targeted singleplex, doubleplex, and tripleplex genomic integration of in vivo assembled DNA parts with efficiencies of 95, 52, and 43%, respectively...
May 24, 2018: Biotechnology Letters
Khalid Shahin, Kim D Thompson, Neil F Inglis, Kevin Mclean, Jose Gustavo Ramirez-Paredes, Sean J Monaghan, Rowena Hoare, Michael Fontaine, Matthijs Metselaar, Alexandra Adams
AIMS: The aims of the current study were to characterise the outer membrane proteins (OMPs) of Francisella noatunensis subsp. orientalis (Fno) STIR-GUS-F2f7, and identify proteins recognised by sera from tilapia, Oreochromis niloticus, (L) that survived experimental challenge with Fno. METHODS AND RESULTS: The composition of the OMPs of a virulent strain of Fno (STIR-GUS- F2f7), isolated from diseased red Nile tilapia in UK, was examined. The sarcosine-insoluble OMP fraction was screened with tilapia hyper-immune sera by western blot analysis following separation of the proteins by 1D SDS-PAGE...
May 19, 2018: Journal of Applied Microbiology
Emily L Kaufman, Nathan E Stone, Glen A Scoles, Crystal M Hepp, Joseph D Busch, David M Wagner
BACKGROUND: The American dog tick, Dermacentor variabilis, is an important vector of pathogens to humans, wildlife and domestic animals in North America. Although this tick species is widely distributed in the USA and Canada, knowledge of its range-wide phylogeographic patterns remains incomplete. METHODS: We carried out a phylogenetic analysis of D. variabilis using samples collected from 26 USA states and five Canadian provinces. Tick samples (n = 1053 in total) originated from two main sources: existing archives (2000-2011), and new collections made from 2012 to 2013...
May 18, 2018: Parasites & Vectors
Haley A Brown, Evgeny Vinogradov, Michel Gilbert, Hazel M Holden
Recent studies have demonstrated that the O-antigens of some pathogenic bacteria such as Brucella abortus, Francisella tularensis, and Campylobacter jejuni contain quite unusual N-formylated sugars (3-formamido-3,6-dideoxy-d-glucose or 4-formamido-4,6-dideoxy-d-glucose). Typically, four enzymes are required for the formation of such sugars: a thymidylyltransferase, a 4,6-dehydratase, a pyridoxal 5'-phosphate or PLP-dependent aminotransferase, and an N-formyltransferase. To date, there have been no published reports of N-formylated sugars associated with Mycobacterium tuberculosis...
May 15, 2018: Protein Science: a Publication of the Protein Society
M Polat, T Karapınar, F Sırmatel
BACKGROUND: Tularaemia is a zoonotic infectious disease caused by Francisella tularensis, an aerobic, uncapsulated, gram-negative coccobacillus. Several case reports have appeared on the dermatological manifestations of tularaemia, but relatively few longer-term studies are available. AIM: To identify skin features of tularaemia that aid in its diagnosis. METHODS: In total, 168 patients (68 male, 100 female) diagnosed with tularaemia were retrospectively examined...
May 14, 2018: Clinical and Experimental Dermatology
Forrest Jessop, Benjamin Schwarz, Emily Heitmann, Robert Buntyn, Tara Wehrly, Catharine M Bosio
Francisella tularensis ssp tularensis (Ftt) is a highly pathogenic intracellular bacterium that suppresses host inflammation by impairing the metabolic shift from oxidative phosphorylation to glycolysis. Decreased mitochondrial metabolism is central to initiating a metabolic shift to glycolysis and regulating inflammation, but Ftt manipulation of host mitochondrial function has not been explored. We demonstrate using extracellular flux analysis that Ftt infection initially improves host macrophage mitochondrial bioenergetics in a capsule dependent manner...
May 14, 2018: Infection and Immunity
Paula Lado, Barbara Qurollo, Cathy Williams, Randall Junge, Hans Klompen
Lemurs are primate species that are endemic to Madagascar. At present, about 90% of lemur species are endangered, and 5 species are among the 25 most endangered primates worldwide. Health status is a major factor impacting the viability of wild populations of many endangered species including lemurs. Given this context, we analyzed the microbiome of 24 specimens of Haemaphysalis lemuris, the most common tick parasitizing lemurs in their native habitats. Ticks were collected from 6 lemur species and microbiomes analyzed using next-generation sequencing...
May 2, 2018: Ticks and Tick-borne Diseases
Eva Špitalská, Olivier Sparagano, Michal Stanko, Katarína Schwarzová, Zdenko Špitalský, Ľudovít Škultéty, Sabína Fumačová Havlíková
Ticks are important vectors of pathogens affecting humans and animals worldwide. They do not only carry pathogens but diverse commensal and symbiotic microorganisms are also present in ticks. A molecular screening for tick-borne pathogens and endosymbionts was carried out in Ixodes ricinus, Dermacentor reticulatus and Haemaphysalis inermis questing ticks collected in Slovakia. The presence of Rickettsia spp., Coxiella burnetii, Coxiella-like and Francisella-like microorganisms was evaluated by PCR in 605 individuals and by randomly sequencing 66 samples...
May 3, 2018: Ticks and Tick-borne Diseases
Daniel L Clemens, Bai-Yu Lee, Marcus A Horwitz
Francisella tularensisis subsp. tularensis is an intracellular bacterial pathogen and the causative agent of the life-threatening zoonotic disease tularemia. The Francisella Pathogenicity Island encodes a large secretion apparatus, known as a Type VI Secretion System (T6SS), which is essential for Francisella to escape from its phagosome and multiply within host macrophages and to cause disease in animals. The T6SS, found in one-quarter of Gram-negative bacteria including many highly pathogenic ones, is a recently discovered secretion system that is not yet fully understood...
2018: Frontiers in Cellular and Infection Microbiology
Jinhong Ren, Tina L Mistry, Pin-Chih Su, Shahila Mehboob, Robel Demissie, Leslie Wo-Mei Fung, Arun K Ghosh, Michael E Johnson
We have previously reported benzimidazole-based compounds to be potent inhibitors of FabI for Francisella tularensis (FtFabI), making them promising antimicrobial hits. Optically active enantiomers exhibit markedly differing affinities toward FtFabI. The IC50 of benzimidazole (-)-1 is ∼100× lower than the (+)-enantiomer, with similar results for the 2 enantiomers. Determining the absolute configuration for these optical compounds and elucidating their binding modes is important for further design. Electronic circular dichroism (ECD) quantum calculations have become important in determining absolute configurations of optical compounds...
April 22, 2018: Bioorganic & Medicinal Chemistry Letters
Qingmei Jia, Richard Bowen, Barbara Jane Dillon, Saša Masleša-Galić, Brennan T Chang, Austin C Kaidi, Marcus A Horwitz
Bacillus anthracis, Yersinia pestis, and Francisella tularensis are the causative agents of Tier 1 Select Agents anthrax, plague, and tularemia, respectively. Currently, there are no licensed vaccines against plague and tularemia and the licensed anthrax vaccine is suboptimal. Here we report F. tularensis LVS ΔcapB (Live Vaccine Strain with a deletion in capB)- and attenuated multi-deletional Listeria monocytogenes (Lm)-vectored vaccines against all three aforementioned pathogens. We show that LVS ΔcapB- and Lm-vectored vaccines express recombinant B...
May 3, 2018: Scientific Reports
Guolin Cui, Jun Wang, Xinyi Qi, Jingliang Su
Francisella tularensis is a facultative intracellular Gram-negative bacterium that causes the zoonotic disease tularemia. We identified the transcription elongation factor GreA as a virulence factor in our previous study, but its role was not defined. Here, we investigate the effects of the inactivation of the greA gene, generating a greA mutant of F. tularensis subsp. novicida. Inactivation of greA impaired the bacterial invasion into and growth within host cells, and subsequently virulence in mouse infection model...
May 2, 2018: Scientific Reports
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